Discontinuation rates and predictors of Medical Cannabis cessation for chronic musculoskeletal pain

Mohammad Khak; Sina Ramtin; Juliet Chung; Asif M. Ilyas; Ari Greis

doi:10.1371/journal.pone.0329897

Peer Review History

Original SubmissionApril 21, 2025
29 May 2025 Decision Letter - Souparno Mitra, Editor PONE-D-25-19383 Discontinuation Rates and Predictors of Medical Cannabis Cessation for Chronic Musculoskeletal Pain PLOS ONE Dear Dr. Ramtin, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. ============================== ACADEMIC EDITOR: Please address reviewer comments and resubmit for consideration for publication ============================== Please submit your revised manuscript by Jul 13 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. 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Note: spreadsheet columns with personal information must be removed and not hidden as all hidden columns will appear in the published file. Additional guidance on preparing raw data for publication can be found in our Data Policy (https://journals.plos.org/plosone/s/data-availability#loc-human-research-participant-data-and-other-sensitive-data) and in the following article: http://www.bmj.com/content/340/bmj.c181.long. 5. We note you have included a table to which you do not refer in the text of your manuscript. Please ensure that you refer to Table 1 in your text; if accepted, production will need this reference to link the reader to the Table. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Partly Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The study titled “Discontinuation Rates and Predictors of Medical Cannabis Cessation for Chronic Musculoskeletal Pain” addresses a timely and important question on medical cannabis (MC) use in chronic musculoskeletal pain, a condition with significant public health burden. This study uniquely examines discontinuation rates and potential predictors, filling a knowledge gap. Data is collected from a clinical MC program, reflecting real-world usage and discontinuation patterns in a regulated environment. Analysis at 3 months and 1 year provides insight into early attrition versus sustained engagement, which is valuable for guiding clinical expectations and patient counseling. However some of the limitations have not been addressed or mentioned in the study: 1. Discontinuation may vary by THC/CBD ratio, method of administration (e.g., tincture vs. vaporized), and side-effect profiles. These key variables were not collected or analyzed. 2. Without tracking pain severity or functional status over time, it's unclear whether discontinuation reflects symptom improvement, lack of efficacy, or adverse effects. 3. Patient expectations and subjective satisfaction are strong predictors of treatment adherence, but these were not assessed. 4. Financial barriers and cannabis availability (e.g., dispensary access, product consistency) may influence discontinuation but are not addressed. 5. Other comorbid conditions (e.g., cognitive impairment, polypharmacy) in older adults could influence discontinuation but were not explored. Please address these limitations in the study. Reviewer #2: Well written article. Please explain and further expand on the various complications arising as a result of medical cannabis use which led to discontinuation of use mainly in the older population. Also an explanation of the types of Medical Cannabis used by the subjects in the study , with mention of the THC:CBD ratio would give a broader understanding of what types of Medical Cannabis were tolerated and which ones were discontinued more. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Nikhil Tondehal Reviewer #2: Yes: Arun Prasad ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. Attachments Attachment Submitted filename: Discontinuation of medical cannabis.pdf https://doi.org/10.1371/journal.pone.0329897.r001
Revision 1
8 Jun 2025 Author Response Dear Editor-in-Chief of PLOS ONE, We sincerely thank you for the opportunity to revise and resubmit our manuscript titled: "Discontinuation Rates and Predictors of Medical Cannabis Cessation for Chronic Musculoskeletal Pain." We appreciate the thoughtful comments provided by the editorial team and peer reviewers. We have revised the manuscript accordingly and addressed each point as detailed below. All changes have been incorporated into the main text per PLOS ONE guidelines. Please find our detailed responses below: Editorial Comments 1. Style and Formatting: Please ensure that your manuscript meets PLOS ONE's style requirements… Response: We have reviewed and revised the manuscript to align with the PLOS ONE formatting style, including the title page, abstract structure, and section headings. 2. Ethics Statement: Please include your full ethics statement in the ‘Methods’ section… Response: We have added the following ethics statement in the “Methods” section: “Patient outcome measures in this study were derived from the Rothman Orthopaedic Cannabis Data Repository (ROCDR), which was established with approval from the Institutional Review Board at Thomas Jefferson University, Philadelphia, Pennsylvania (protocol number 19D.159). Verbal consent was obtained from all participants prior to data collection.” 3. Data Availability – Third-Party Data: Please describe the data source, confirm usage permission, disclose any special access, and provide contact info for data access. Response: We have included the following statement in the Data Availability section: “The data used in this study were obtained from the Rothman Orthopaedic Cannabis Data Repository (ROCDR), a third-party dataset managed by the Rothman Institute Foundation for Opioid Research & Education. The authors do not have permission to publicly share the full dataset. However, interested researchers may apply for access by contacting the Rothman Institute Foundation at mohammad.khak@rothmanopioid.org. The authors did not receive any special privileges in accessing this dataset.” 4. Data Anonymization: Remove personal information and re-upload an anonymized dataset. Response: As outlined in our Data Availability Statement (Editorial Comment #3), the dataset used in this study is part of the Rothman Orthopaedic Cannabis Data Repository (ROCDR), a third-party database we do not have legal rights to publicly share. Therefore, no dataset has been uploaded. 5. Missing Table Reference: Refer to Table 1 in the text. Response: We have added a reference to Table 1 in the Results section. Reviewer Comments Reviewer #1 We appreciate the reviewer’s valuable feedback. We have added a new paragraph in the Discussion section addressing the following limitations. We also added a reference to a similar recently published article addressing part of these limitations in a prospective study. Reviewer #2 Comment 1: Please expand on complications in older patients that may have led to discontinuation. Response: We added the following paragraph to the Discussion section: “Although our study did not collect detailed data on adverse effects, this trend may be partially explained by age-related concerns such as increased susceptibility to cognitive side effects, dizziness, or drug interactions. One possible explanation for the higher discontinuation rates observed in the elderly population is the presence of more advanced musculoskeletal conditions, which may not respond well to medical cannabis.” ________________________________________ Reviewer #2 Comment 2: Explain types of cannabis used and include THC:CBD ratios. Response: We acknowledge this limitation. Unfortunately, detailed data on product formulation and THC:CBD ratios were not consistently available in patient records. We have noted this as a limitation in the Methods and Discussion and highlighted the need for future research that includes specific product characteristics to better understand their impact on treatment adherence. Attachments Attachment Submitted filename: long-term, stable access to study data contact.docx https://doi.org/10.1371/journal.pone.0329897.r002
3 Jul 2025 Decision Letter - Souparno Mitra, Editor PONE-D-25-19383R1 Discontinuation Rates and Predictors of Medical Cannabis Cessation for Chronic Musculoskeletal Pain PLOS ONE Dear Dr. Ramtin, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please address reviewer comments and resubmit to reconsider for publication. Please submit your revised manuscript by Aug 17 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Souparno Mitra, M.D. Academic Editor PLOS ONE Journal Requirements: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #2: All comments have been addressed Reviewer #3: (No Response) ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #2: Partly Reviewer #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: Yes Reviewer #3: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #2: Yes Reviewer #3: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #2: Yes Reviewer #3: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #2: Thank you for addressing the suggested edits for "Discontinuation Rates and Predictors of Medical Cannabis Cessation for Chronic Musculoskeletal Pain." Reviewer #3: “scores were collected at baseline”. Recommend substituting Baseline with before intervention. “Executive function” includes Working Memory and selective attention “history of substance abuse or severe mental health disorders”. Substance abuse is mental health disorder when they meet criteria per DSM-V Include PROMIS 10 questionnaires using 5-point Likert scales. Rating is “limited to the past 7 days” before intervention. “There was a significant difference in age between the two groups” Statistically significant Reference for “advanced musculoskeletal conditions which may not respond well to medical cannabis” “Advanced musculoskeletal conditions in the elderly” such as degenerative changes (radiculopathies, stenosis) or chronic wear and tear(OA, tendinopathies etc) “That study.” Please reference the study here “due to its retrospective design”. Does 2-year follow-up after an intervention(MC) make it a prospective rather than a retrospective study? ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #2: Yes: Arun Prasad Reviewer #3: Yes: Anoop Narahari ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0329897.r003
Revision 2
8 Jul 2025 Author Response Dear Editor-in-Chief of PLOS ONE, We sincerely thank you for the opportunity to revise and resubmit our manuscript titled: "Discontinuation Rates and Predictors of Medical Cannabis Cessation for Chronic Musculoskeletal Pain." We appreciate the thoughtful comments provided by the editorial team and peer reviewers. We have revised the manuscript accordingly and addressed each point as detailed below. All changes have been incorporated into the main text per PLOS ONE guidelines. Please find our detailed responses below: Reviewer#2 Comments: 1. “scores were collected at baseline”. Recommend substituting Baseline with before intervention. Response: Corrected. The term “baseline” has been replaced with “before intervention” throughout the manuscript. 2. “Executive function” includes Working Memory and selective attention Response: We have revised the manuscript to remove specific mentions of “working memory” and “selective attention” under “executive function” to improve clarity and accuracy. 3. “history of substance abuse or severe mental health disorders”. Substance abuse is a mental health disorder when it meets DSM-V criteria Response: Thank you for the clarification. The sentence has been updated to: “significant history of substance abuse or any other mental health disorders” to align with DSM-V definitions. 4. Include PROMIS 10 questionnaires using 5-point Likert scales. Rating is “limited to the past 7 days” before intervention. Response: We have added a reference to the questionnaire, which is available online at https://www.healthmeasures.net/. 5. “There was a significant difference in age between the two groups” – Statistically significant Response: We have updated the sentence to read: “There was a statistically significant difference in age between the two groups.” 6. Reference for “advanced musculoskeletal conditions which may not respond well to medical cannabis” Response: A supporting reference has been added to the manuscript to substantiate this statement. 7. “Advanced musculoskeletal conditions in the elderly” such as degenerative changes (radiculopathies, stenosis) or chronic wear and tear (OA, tendinopathies etc) Response: We have incorporated these specific examples—radiculopathies, stenosis, osteoarthritis (OA), and tendinopathies—into the manuscript to provide clarity. 8. “That study.” Please reference the study here Response: The study has been referenced as citation [15], and the sentence has been rephrased accordingly. 9. “due to its retrospective design”. Does 2-year follow-up after an intervention (MC) make it a prospective rather than a retrospective study? Response: To eliminate confusion, we have removed this sentence from the manuscript. Attachments Attachment Submitted filename: point by point response 2nd.docx https://doi.org/10.1371/journal.pone.0329897.r004
23 Jul 2025 Decision Letter - Souparno Mitra, Editor Discontinuation Rates and Predictors of Medical Cannabis Cessation for Chronic Musculoskeletal Pain PONE-D-25-19383R2 Dear Dr. Ramtin, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. 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If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #2: All comments have been addressed Reviewer #3: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #2: Yes Reviewer #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: Yes Reviewer #3: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #2: Yes Reviewer #3: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #2: Yes Reviewer #3: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #2: Thank you for making the suggested edits. Best of luck on publication of "Discontinuation Rates and Predictors of Medical Cannabis Cessation for Chronic Musculoskeletal Pain. Reviewer #3: (No Response) ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #2: Yes: Arun Prasad Reviewer #3: Yes: Anoop Narahari ******** https://doi.org/10.1371/journal.pone.0329897.r005
Formally Accepted
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